With the adoption of western diets in recent years more high-fat foods have become available, leading to an increase in the incidence of such lifestyle-related diseases as hypercholesterolemia, hyperlipidemia and arteriosclerosis. Symptoms of hyperlipidemia accompanying elevated total blood cholesterol and low-density lipoprotein (LDL) cholesterol are known to be an important risk factor for atherosclerotic cardiovascular disease (Assman, G. et al., Circulation, 1999, 100, 1930 to 1938; Grundy, S. et al., Circulation, 1999, 100, 1134 to 1146).
Methods of reducing blood cholesterol by interfering with the circulation of bile acids through the intestines have been established for ameliorating hyperlipidemia. Specific examples of such methods include treatment with HMG-CoA reductase inhibitors, preferably statin drugs such as simvastatin and fluvastatin, and treatment with bile acid sequestrants such as anion exchange resins.
These drugs are used world-wide as cholesterol-lowering agents (or lipid-lowering agents), and of these, statin drugs command a roughly 80 to 90% share of the market for hyperlipidemia treatment, and their effectiveness has been established as the drugs of choice for hypercholesterolemia. In recent years, however, side-effects such as muscle disorders (rhabdomyolysis), liver function disorders (liver enzyme elevation, etc.), neural disorders and the like have been reported which are common to statin drugs, and there are concerns about safety with long-term use (Clinics in Liver Disease, 2003, 7, 415 to 433; Current Therapy, 1999, Vol. 19, No. 9, 53 to 56; Donaghy M., Neurology, 2002, 58, 1321 to 1322; Gaist, D. et al., Neurology, 2002, 58, 1333 to 1337). Cholesterol levels are also seen to rebound after the drug is stopped, making it difficult to stop the drug. The reality now is that it may be impossible to stop administering statin drugs despite the awareness of side-effects, and if they are stopped patients may be forced to go on low-cholesterol diets, detracting markedly from quality of life.